Aguilar-Navarro S, Ávila-Funesa JA

Idioma: Español
Referencias bibliográficas: 189
Paginas: 141-148
Archivo PDF: 77.47 Kb.

RESUMEN

La depresión es uno de los principales síndromes geriátricos. Es una enfermedad crónica o recurrente que tiene consecuencias devastadoras en el adulto mayor. La prevalencia es diferente según la metodología y la población de referencia utilizada, pero puede ser del 10 al 27%. En Estados Unidos, la depresión genera un gasto anual de 43 mil millones de dólares y los ancianos deprimidos parecen tener una mayor susceptibilidad para las enfermedades crónicas y el deterioro funcional.
Las manifestaciones de la depresión en el anciano son fluctuantes y los síntomas somáticos tales como la fatiga, el insomnio y la anorexia predominan pero con poca especificidad ya que muchos adultos mayores, sin depresión, los pueden presentar. La detección temprana es deseable siempre y cuando los instrumentos usados para ello sean válidos y confiables.
En este artículo se revisan las características clínicas sobresalientes y las consecuencias de la depresión en el adulto mayor. Además, se muestran las principales características metrológicas del instrumento más utilizado para su detección: la escala de depresión geriátrica(EDG). Una mejor comprensión de este problema permitirá un diagnóstico temprano y un tratamiento oportuno.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Murray A, y Hunt T. The cell cycle. An Introduction. Oxford University Press. 1993.

2. Johnson DG, Walker CL. Cyclins and cell cycle chekpoints. Ann Rev Pharmacol Toxicol 1999;39:295-312.

3. Israels ED, Israels LG. The Cell cycle. Stem Cells 2001;19:88-91.

4. Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nature Reviews 2001;1:222-231.

5. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG. The Clustal X Windows interface: flexible strategies for multiple sequence alignment by quality analysis tools. Nucleic Acids Res 1997;24:4876-4882.

6. Russell P. y Nurse P. Shizosaccharomyces pombe and Saccharomyces cerevisiae: a look at yeasts divided. Cell 1986; 45:781-782.

7. Malumbres M, Barbacid M. Mammalia cyclin-dependent kinases. Trends Biochem. Sci 2005;30:630-41.

8. Conget PA, Mingell JJ. Adenoviral-mediated gene transfer into ex vivo expanded human bone marrow mesenchymal progenitor cells. Exp Hematol 2000;28:382-90.

9. Aleemet E, Kiyokawa H, Kaldis P. Cdc2-cyclin E complexes regulate the G1/ S phase transition. Nat. Cell Biol 2005;7:831-836.

10. Malumbres M, Sotillo R, Santamaria D, Galan J, Cerezo A, Ortega S, et al. Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6. Cell 2004;118:493-504.

11. Ren S, Rollins BJ. Cyclin/Cdk3 promotes Rb-dependent Go exit. Cell 2004;117:239-251.

12. Lilja L, Johansso JU, Gromada J, Mandic SA, Fried G, Berggeren PO, et al. Cyclin-dependenst kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+) dependent exocytosis. J. Biol Chem 2004;279:29534-29541.

13. Zhang L, Gjoerup O, Roberts TM. Serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling. Proc. Natl. Acad. Sci 2004;101:10296-10301.

14. Lolli G, Johnson LN. CAK-cyclin-dependent activating kinase: a key kinase in cell cycle control and atarget for drugs? Cell Cycle 2005;4:572-577.

15. Akoulitchev S, Chuikov S, Reinberg D. TFIIH is negatively regulated by cdk8- containing mediator complexes. Nature 2000;407:102-106.

16. Garriga J, Graña X. Cellular control of gene expression by T-type cyclin/CDK9 complexes. Gene 2004;337:15-23.

17. Kasten M, Giordano A. Cdk10, a Cdc2-related kinase, associates with the Ets2 transcription factor and modulates its transactivation activity. Oncogene 2001;20:1832-1838.

18. Loyer P, Trembley JH, Katona R, Kidd VJ, Lahti JM. Role of CDK/cyclin complexes in transcription and RNA splicing. Cell. Signal. 2005;17:1033-1051.

19. Roberts M.J. Evoling ideas about cyclins. Cell 1999;98:129-132.

20. Evans T, Rosenthal ET, Younglom J, Distel D, Hunt T. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 1983;33:389-396.

21. Hunt T. Maturation promoting factor, cyclin and the control of M-phase. Curr. Opin. Cell Biol 1989;1:268-274.

22. Nurse P. Universal control mechanism regulating onset of M-phase. Nature 1990;344:503-508.

23. Xiog Y, Beach D. Population explosion in the cyclin family. Curr. Biol 1991;1:362-364.

24. Peter M. The regulation of cycli-dependen kinase inhibitors (CKIs). Prog Cell Cycle Res 1997;3:99-108.

25. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993;366:704-707.

26. Hannon GJ, Beach D. p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 1994;371:257-261.

27. Guan KL, Jenkins CW, Li Y, Nichols MA, Wu X, O´Keefe CL, et al. Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function.Genes Dev 1994;8:2939-2952.

28. Chan FK, Zhang L, Chen L, Shapiro DN, Winoto A. Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4. Mol. Cell. Biol 1995;15:2682-2688.

29. Parry D, Mahony D, Wills K, Lees E. Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. Mol. Cell. Biol 1999;19:1775-1783.

30. Thullberg M, Bartkota J, Khan S, Hansen K, Ronnstrand L, Lukas J, Strauss M, Bartek J. Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors. FEBS Lett 2000;470:161-166.

31. Jeffrey PD, Tong L, Pavletich NP. Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors. Genes Dev 2000;14:3115-3125.

32. Ly Y, Nichols MA, Shay JW, Xiong Y. Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb. Cancer Res 1994;54:6078-6082.

33. Gu Y, Turk CW, Morgan DO. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature 1993;366:634-635.

34. Noda A, Ning Y, Venable SF, Pereira-Smith OM, Smith JR. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell Res 1994;211:90-98.

35. Poliak K, Kato J, Solomon MJ, Ser CJ, Massague J, Roberts JM, et al. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev 1994;8:9-22.

36. Matsuoka S, Edwards MC, Bai C, Parquer S, Zhang P, Baldini A, et al. p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev 1995;9:650-662.

37. Chen J, Jackson PK, Kirschner MW, Dutta A. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature 1995;374:386-388.

38. Russo AA, Jeffrey PD, Patten AK, Massague J, Pavletich NP. Crystal structure of the p27Kip1 cyclin-dependent kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 1996;382:325-331.

39. Pei XH, Xiog Y. Biochemical and cellular mechanisms of mammalian CDK inhibitors: a few unresolved issues. Oncogene 2005;24:2787-2795.

40. Feng XH, Lin X, Derinck R. Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15 (Ink4B) transcription in response to TGF-beta. EMBO J 2000;19:5178-5193.

41. Nevis JR. Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ1998;9:585-593.

42. Cam H, Dynlancht BD. Emerging roles for E2F: beyond the G1/S transition and DNA replication. Cancer Cell 2003;3:311-316.

43. Dyson, N. The regulation of E2F by pRB-family proteins. Genes Dev 1998;12:2245-2262.

44. Aslanian A, Iaquinta PJ, Verona R, Lees JA. Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics. Genes Dev 2004;1413-1422.

45. Trimarchi JM, Lees JA, Sibling rivalry in the E2F family. Nat. Rev. Mol. Cell. Biol. 2002;3:11-20.

46. Kherrouche Z, De Launoit Y, Monte D. Human E2F6 is alternatively spliced to generate multiple protein isoforms. Biochem. Biophys. Res. Commun 2004;317:749-760.

47. Tsai KY, HY, Macleof KF, Crowley DY, Yamasaki L, Jacks T. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry ad extends survival of Rb-deficient mouse embryos. Moll Cell 1998;2:293-304.

48. Lacey KR, Jackson PK, Stearns T. Ciclin-dependent kinase control of centrosome duplication. Proc Natl Acad Sci USA 1999;96:2817-2822.

49. Zhao J, Kennedy BK, Lawrece BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links clyclin E-Cdk2 to the regulation of replication-dependent histone gene. Genes Dev 2000;14:2283-2297.

50. Zhao J, Dynlacht B, Imai T, Hori T, Harlow W. Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entry. Genes Dev 1998;12:456-461.

51. Bouchar C, Staller P, Eilers M. Control of cell proliferation by Myc. Trends in Cell Biology 1998;8:202-206.

52. Nasi S, Ciarapica R, Jucker R, Rosati J, Soucek L. Making decisions through Myc. FEBS Letters 2001;490:153-162.

53. Blagosklonny MV, Pardee AB. The restriction point of cell cycle. Cell Cycle 2002;2:103-110.

54. Zetterberg A, Larsson O, Wiman KG. What is the restriction point? Curr Opin Cell Biol 1995;7:835-842.

55. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular biology of the cell. Garland Publishing, Inc. New York U.S.A., 1994.

56. Marshall MS. Ras target proteins in eukaryotic cells. FASEB J 1995;9:1311-1318.

57. Lavoie JN, L’Allemain G, Brunet A, Muller R, Pouyssegur J. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem 1996;271:20608-20616.

58. Cheng M, Sexl V, Sherr CJ, Roussel MF. Assambly of cyclin D-dependent kinase and titration of p27kip1 regulated by mitogen-activated protein kinase (MEK1). Proc Natl Acad Sci USA 1998;95:1091-1096.

59. Golias CH, Charalabopoulos A, Charalabopoulos K. Cell proliferation and cell control: a mini review. Int j Clin Pract 2004;12:1134-1141.

60. Nasheuer HP, Smith R, Bauerschmidt C, Grosse F, Weisshark K. Initiation of eukaryotic DNA replication: regulation and mechanisms. Prog Nucleic Acid Res Mol Biol 2002;72:41-91.

61. Iizuka M, Stillma B. Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein. J Biol Chem 1999;274:23027-23034.

62. Findeisen M, E1-Denary M, Kapitza T, Graf R, Strausfeld U. Ciclin Adependent kinase activity affects chromatin binding of ORC, Cdc6 and MCM in egg extracts of Xenopus laevis. Eur J Biochem 1999;264:415-426.

63. Ishimi Y. A DNA helicase activity is associated with a MCM4, -6 and 7 protein complex. J Biol Chem 1997;272:24508-24513.

64. Sanchez I, Dylcht BC. New insights into cyclins, CDKs, and cell cycle control. Semin Cell Dev Biol 2005;16:311-321.

65. Ferby I, Blazquez M, Palmer A, Eritja R, Nebreda AR. A novel p34 (cdc2)-binding and activating protein that is necessary and sufficient to trigger G(2)/M progression in Xenopus oocytes. Genes Dev 1999;13:2177-2189.

66. Ookata K, Hisanaga S, Okumura E, Kishimoto T. Association of p34cdc2/ciclin B complex with microtubules in star fish oocytes. J Cell Sci 1993;105:873-881.

67. Mayani H, Guilbert LJ, Janowska-Wieczorek A. Biology of the hemopoietic microenvironment. Eur J Haematol 1992;34:49:225-233.

68. Bhatia M, Bonnet D, Murdoch B, Gan OI, Dick JE. A Newly discovered class of human hematopoietic cells with SCID repopulating activity. Nat Med 1998;4:1038-1045.

69. Morrison SJ, Wright DE, Cheshier SH, Weissman IL. Hematopoietic stem cells: challenges to expectations. Curr Opin Immunol 1997;216-221.

70. Mayani H, Alvarado-Moreno JA, Flores-Guzman P. Biology of human hematopoietic stem and hematopoietic stem and progenitor cells present in circulation. Arch Med Res 2003;476-488.

71. Cheng T, Rodrigues N, Dombkowski D, Stier S, Scadden DT. Stem cell repopulation efficiency but not pool size is governed by p27kip1. Nature Med 2000;6:1235-1240.

72. Rosedaal M, Adam J. Haemopoiesis by clonal succession? Blood Cells 1984;10:473-485.

73. Quesenberry PJ, Colvin GA, Lambert JF. The chiaroscuro stem cell: a unified stem cell theory. Blood 2002;100:4266-4271.

74. Serr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 1995;9:1149-1163.

75. Taniguchi T, Endo H, Chikatsu N, Uchimaru K, Asano S, Fujita T, et al. Expression of p21 (Cip1/Waf1/Sdi1) and p27 (kip) cyclin-dependent kinase inhibitors during human hematopoiesis. Blood 1999;93:4167-4178.

76. Tschan MP, Peters UR, Cajot JF, Betticher DC, Fey MF, Tobler A. The cyclidependent kinase inhibitors p18IK4c and p19INK4d are highly expressed in CD34+ progenitor and acute myeloid leukaemic cells but not I normal differentiated myeloid cells. Br J Haematol 1999;106:644-651.

77. Yaroslavskiy B, Watkins S, Doneberg AD, Patto TJ, Steinman RA. Subcellular and cell-cycle expression profiles of CDK-inhibitors in normal differentiating myeloid cells. Blood 1999;93:2907-2917.

78. Marone M, Pierelli L, Mozzetti S, Mascuillo V, Boanno G, Morosetti R, Rutella S, Battaglia A, Rumi C, Mancuso S, Leone G, Giordano A, Scambia G. High cyclin-dependent kinase inhibitors in Bcl-2 and Bcl-xL- expressing CD34+- proliferating haematopoietic progenitors. Br J Haematol 2000;110:654- 662.

79. Ducos K, Panterne B, Fortunel , Hatzfeld A, Monier MN, Hatzfeld J. p21 (cip1) mRNA is controlled by endogenous transforming growth factor-beta1 in quiescent human hematopoietic cells. J Cell Physiol 2000;184:80-85.

80. Stier S, Cheng T, Forkert R, Lutz C, Dombkowski DM, Zhang JL, Scadden DT. Ex vivo targeting of p21 Cip/Waf1 permits relative expansion of human hematopoietic stem cells. Blood. 2003;1260-1266.

81. Summers YJ, Heyworth CM, Wynter EA, Chang J, Testa NG. Cord blood Go CD34+ cells have a thousand-fold higher capacity for generating progenitors in vitro than G1 CD34+ cells. Stem Cells 2001;19:505-513.

82. Mayani H, Lansdorp PM. Biology of human umbilical cord blood-derived hematopoietic stem/progenitor cells. Stem Cells 1998;16:153-165.

83. Lewis ID, Verfaillie CM. Multi-lineaje expansion potential of hematopoietic progenitors: superiority of umbilical cord blood compared to mobilized peripheral blood. Exp Hematol 2000;28:1087-1095.

84. Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradkey A, et al. P53 independent expression of p21 Cip 1 in muscle and other terminally differentiating cells. Science 1995;1024-1027.

85. Durand B, Gao FB, Raff M. Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J 1997;16:306-317.

86. Mantel C, Luo Z, Cafield J, Braun S, Deng C, Broxmeyer HE. Involvement of p21 cip-1 ad p27 kip-1 in the molecular mechanisms of steel factor-induced proliferative synergy in vitro and of p21 cip-1 in the maintenance of stem/progenitor cells in vivo. Blood 1996;88:3710-3719.

87. Zeng YX, e-Deiry WS. Regulation of p21 WAF1/CIP1 expression by p53- independent pathways. Oncogene. 1996;12:1557-1564.

88. Zhang W, Grasso L, McClain CD, Gambel AM, Cha Y, Travali S, et al. p53- independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation Cancer Research 1995;55:668-674.

89. Steinman RA, Lu Y, Yarolavskiy B, Stehle C. Cell cycle-independent upregulation of p27Kip1 by p21Waf1 in K562 cells. Oncogene. 2001;20:6524-6530.

90. Steinman RA, Hoffman B, Iro A, Guillouf C, Liebermann DA, el-Houseini ME. Induction of p21 (WAF-1/CIP1) during differentiation. Oncogene 1994,11:3389-3396.

91. Matsumura I, Ishikawa J, Nakajima K, Oritani K, Tomiyama Y, Miyagawa J, et al. Thrombopoietin-induced differentiation of a human megakarioblastic leukemia cell line, CMK, involves transcriptional activation of p21 (WAF/CIP1) by Stat5. Mol Cell Biol 1997;17:2933-2943.

92. Kikuchi I, Furukawa Y, Iwase S, Terui Y, Nakamura M, Kitagawa S, et al. Poliploidization and functional maturation are two distinct processes during megakaryocytic differentiation: Involvement of cyclin-dependent kinase inhibitor p21 in polyploidization. Blood 1997;89:3980-3990.

93. Uchimaru K, Taniguchi T, Yoshikawa M, Fujinuma H, Fujita T, Motokura T. Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor seppressor- mediated pathway. Leukemia Research 1998;22:413-420.

94. Matsuoka M. Nishimoto I. Asano S. Interferon-β impairs physiologic downregulation of cyclin-dependent kinase inhibitor, p27Kip1, during G1 phase progression in macrophages. Exp. Hematol 1999;27:203-209.

95. Tamir A, Petrocelli T, Stetler K, Chu W, Howard J, Croix BS, et al. Stem cell factor inhibits erythroid differentiation by modulating the activity of G1-cyclindependent kinase complexes: a role for p27 in erythroid differentiation coupled G1 arrest. Cell Growth Differentiation 2000;11:269-277.

96. Ghanem L, Steinman RA. p21Waf1 inhibits granulocytic differentiation of 32Dcl3 cells. Leuk Res 2006; (Epub ahead of print).

97. Steinman RA, Huang J, Yaroslavskiy B, Goff JP, Ball ED, Nguyen A. Regulation of p21 (WAF1) expression during normal myeloid differentiation. Blood 1998;91:4531-4542.

98. Baccini V, Roy L, Vitrat N, Chagraoui H, Sabri S, Le Couedic JP, et al. Role of p21 (Cip1/Waf1) in cell cycle exit of endomitotic megakaryocytes. Blood 2001;98:3274-3282.

99. Steinman RA, Yaroslavskiy B, Goff JP, Alber SM, Watkins S. Cdk-inhibitors and exit from quiescence in primitive haematopoietic cell subsets. Br. J. Haematol. 2004;3:358-365.

100. Walkley CR, Fero ML, Chien WM, Purton LE, McArthur GA. Negative cellcycle regulators cooperatively control self-renewal and differentiation of haematopoietic. Nat Cell Biol 2005;2:172-178.

101. Furukawa Y, Kikuchi J, Nakamura M, Iwase S, Yamada H, Matsuda M. Lineage specific regulation of cell cycle control gene expression during haematopoietic cell differentiaon. Br. J. Haematol 2000;110:663-673.

102. Stepanova L, Sorrentino BP. A limited role for p16InK4a y p19Arf in the loss hematopoietic stem cells. Blood 2005;106:827-832.

103. Yu H, Yuan Y, Shen H, Cheng T. Hematopoietic stem cell exhaustion impacted by p18INK4C and p21/Cip1/Waf1 in opposite manners. Blood 2006;3:1200-1206.

104. Yuan Y, Shen H, Franklin DS, Scadden DT, Cheng T. In vivo self-renewing divisions of maematopoietic stem cells are increased in the absence of the early G1-phase inhibitor, p18INK4C. Nat Cell Biol. 2004;5:436-442.

105. Fortunel NO, Hatzfeld JA, Monier MN, Hatzfeld A. Control of hematopoietic stem/progenitor cell fate by transforming growth factor-beta. Oncol. Res 2003;13:445-453.

106. Pierelli L, Marone M, Bonanno G, Mozzetti S, Rutella S, Morosetti R, et al. Modulation of bcl-2 and p27 in human primitive proliferating hematopoietic progenitors by autocrine TGF-β1 is a cell cycle-independent effect and influences their hematopoietic potential. Blood 2000;95:3001-3010.

107. Teofili L, Morosetti R, Martini M, Urbano R, Putzulu R, Rutella S, et al. Expression of cyclin-dependent kinase inhibitor p15(INK4B) during normal and leukemic myeloid differentiation. Exp Hematol 2000;28:519-526.

108. Hamilton M. A raiting scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.

109. Beck AT. Ward CH, Mendelson M. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561-571.

110. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982-1983;17:37-49.

111. Beekman AT, Deeg DJ, van Tilburg T, Smit JH, Hooijer C, van Tilburg W. Major and minor depression in later life: a study of prevalence and risk factors. J Affect Disord 1995;36:65-75.

112. Kay DW, Henderson AS, Scott R, Wilson J, Rickwood D, Grayson DA. Dementia and depression among the elderly living in the Hobart community: the effect of the diagnostic criteria on the prevalence rates. Psychol Med 1985;15:771-788.

113. Copeland JR, Dewey ME, Wood N, Searle R, Davidson IA, McWilliam C. Range of mental illness among the elderly in the community. Prevalence in Liverpool using the GMS-AGECAT package. Br J Psychiatry 1987;150:815-823.

114. Livingston G, Hawkins A, Graham N, Blizard B, Mann A. The Gospel Oak Study: prevalence rates of dementia, depression and activity limitation among elderly residents in inner London. Psychol Med 1990;20:137-146.

115. Penninx BW, Guralnik JM, Ferrucci L, Simonsick EM, Deeg DJ, Wallace RB. Depressive symptoms and physical decline in community-dwelling older persons. JAMA 1998;279:1720-1726.

116. Sheline YI, Mintun MA, Moerlein SM, Snyder AZ. Greater loss of 5-HT(2A) receptors in midlife than in late life. Am J Psychiatry 2002;159:430-435.

117. Kronfol Z, House JD. Depression, cortisol, and immune function. Lancet 1984;1:1026-1027.

118. Miller AH, Spencer RL, McEwen BS, Stein M. Depression, adrenal steroids, and the immune system. Ann Med 1993;25:481-487.

119. Stein M, Miller AH, Trestman RL. Depression, the immune system, and health and illness. Findings in search of meaning. Arch Gen Psychiatry 1991;48:171-177.

120. Ader R, Cohen N, Felten D. Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet 1995;345:99-103.

121. Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB. The role of corticotropinreleasing factor in depression and anxiety disorders. J Endocrinol 1999;160:1-12.

122. Davis KL, Davis BM, Mathe AA, Mohs RC, Rothpearl AB, Levy MI, et al. Age and the dexamethasone suppression test in depression. Am J Psychiatry 1984;141:872-874.

123. Seidman SN, Araujo AB, Roose SP, Devanand DP, Xie S, Cooper TB, et al. Low testosterone levels in elderly men with dysthymic disorder. Am J Psychiatry 2002;159:456-459.

124. Hickie I, Scott E, Naismith S, Ward PB, Turner K, Parker G, et al. Late-onset depression: genetic, vascular and clinical contributions. Psychol Med 2001;31:1403-1412.

125. Blazer DG, Burchett BB, Fillenbaum GG. APOE epsilon4 and low cholesterol as risks for depression in a biracial elderly community sample. Am J Geriatr Psychiatry 2002;10:515-520.

126. Murphy GC, Hollander SB, Rodrigues HE, Kremer CH, Schatzberg AF. Effects of the Serotonin Transporter Gene Promotor Polymorphism on Mirtazapina and Paroxetine. Efficacy and Adverse Events in Geriatric. Arch Gen Psychiatry 2004;61:1163-1169.

127. Lenze EJ, Munin MC, Ferrel RE, Pollock BG, Skidmore E, Lotrich F, et al. Association Transporter Gene-Linked Polymorphic Region (5-HTTLPR) Genotype with Depression in Elderly Person After Hip Fracture. Am, J. Geriatr Psychiatry 2005;13:15.

128. Zill P, Padberg F, De Jonge S,Hampel H, Bürger K, Stübner S, et al. Serotonin transporter (5-HTT) gene polymorphism in psychogeriatric patients. Neurosci Lett. 2000;284:114-115.

129. Kraaij V, de Wilde EJ. Negative life events and depressive symptoms in the elderly: a life span perspective. Aging Ment Health 2001;5:84-91.

130. Devanand DP, Kim MK, Paykina N, Sackeim HA. Adverse life events in elderly patients with major depression or dysthymic disorder and in healthycontrol subjects. Am J Geriatr Psychiatry 2002;10:265-274.

131. Chi I, Chou KL. Social support and depression among elderly Chinese people in Hong Kong. Int J Aging Hum Dev 2001;52:231-252.

132. George LK, Blazer DG, Hughes DC, Fowler N. Social support and the outcome of major depression. Br J Psychiatry 1989;154:478-485.

133. Fonda SJ, Wallace RB, Herzog AR. Changes in driving patterns and worsening depressive symptoms among older adults. J Gerontol B Psychol Sci Soc Sci 2001;56:S343-351.

134. Braam AW, Van den Eeden P, Prince MJ, Beekman AT, Kivela SL, Lawlor BA, et al. Religion as a cross-cultural determinant of depression in elderly Europeans: results from the EURODEP collaboration. Psychol Med 2001;31:803-814.

135. McDowell I, Kristjansson E, Newell C. Depression. In: McDowell I, Newell C, editors. Measuring Health: A guide to rating scales and questionnaires. Second edition ed. New York, USA: Oxford University Press, 1996:238-286.

136. Green J. Neuropsychological evaluation of the older adult: a clinician's guidebook. USA: Academic press, 2000:169-180.

137. Geerlings SW, Beekman AT, Deeg DJ, Twisk JW, Van Tilburg W. The longitudinal effect of depression on functional limitations and disability in older adults: an eight-wave prospective community-based study. Psychol Med 2001;31:1361-1371.

138. Bruce ML, Seeman TE, Merrill SS, Blazer DG. The impact of depressive symptomatology on physical disability: MacArthur Studies of Successful Aging. Am J Public Health 1994;84:1796-1799.

139. Fogel BS, Fretwell M. Reclassification of depression in the medically ill elderly. J Am Geriatr Soc 1985;33:446-448.

140. Mueller TI, Kohn R, Leventhal N, Leon AC, Solomon D, Coryell W, et al. The course of depression in elderly patients. Am J Geriatr Psychiatry 2004;12:22-29.

141. Desautels R. Traitement de la dépression en gériatrie. In: Allard JHPPM, editor. Vieillissement et problèmes de santé mentale. Actes du congrès scientifique, Sherbrooke 2003. Sherbrooke, Canada: EDISEM, 2004.

142. Norman MA, Whooley ME, Lee K. Depression and other mental health issues. In: Landefeld CS, Palmer RM, Johnson MA, Johnston CB, Lyons WL, editors. Current Geriatric Diagnosis and treatment. International edition : McGraw-Hill, 2004:100-113.

143. Sheikh JL, Yesavage J.A. Geriatric Depression Scale (GDS). Recent evidence and development of a shorter version. Clin Gerontol 1986;5:165-172.

144. Almeida OP, Almeida SA. Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV. Int J Geriatr Psychiatry 1999;14:858-865.

145. Rinaldi P, Mecocci P, Benedetti C, Ercolani S, Bregnocchi M, Menculini G, et al. Validation of the five-item geriatric depression scale in elderly subjects in three different settings. J Am Geriatr Soc 2003;51:694-698.

146. Brink TL, Yesavage JA, Lum O. Heersema PH, Adey M, Rose TL. Screening tests for geriatric depression. Clin Gerontol 1982;1:37-43

147. Martínez de la Iglesia J, Onis Vilches MC, Duenas Herrero R, Aguado Taberne C, Albert Colomer C, Arias Blanco MC. [Abbreviating the brief. Approach to ultra-short versions of the Yesavage questionnaire for the diagnosis of depression]. Aten Primaria 2005;35:14-21.

148. Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1977;1:385-401.

149. World Health Organization. International classification of diseases (ICD) 10th Revision 2003 [Sitio en Internet]. Hallado en: http://www3.who.int/icd/vol1htm2003/fr-icd.htm Acceso el 1 de diciembre de 2005.

150. Penninx BW, Leveille S, Ferrucci L, van Eijk JT, Guralnik JM. Exploring the effect of depression on physical disability: longitudinal evidence from the established populations for epidemiologic studies of the elderly. Am J Public Health 1999;89:1346-1352.

151. Roberts RE, Kaplan GA, Shema SJ, Strawbridge WJ. Prevalence and correlates of depression in an aging cohort: the Alameda County Study. J Gerontol B Psychol Sci Soc Sci 1997;52:S252-258.

152. Cronin-Stubbs D, de Leon CF, Beckett LA, Field TS, Glynn RJ, Evans DA. Six-year effect of depressive symptoms on the course of physical disability incommunity-living older adults. Arch Intern Med 2000;160:3074-3080.

153. Luber MP, Meyers BS, Williams-Russo PG, Hollenberg JP, DiDomenico TN, Charlson ME, et al. Depression and service utilization in elderly primary care patients. Am J Geriatr Psychiatry 2001;9:169-176.

154. Morley JE, Kraenzle D. Causes of weight loss in a community nursing home. J Am Geriatr Soc 1994;42:583-585.

155. Alexopoulos GS, Vrontou C, Kakuma T, Meyers BS, Young RC, Klausner E, et al. Disability in geriatric depression. Am J Psychiatry 1996;153:877-885.

156. Romanelli J, Fauerbach JA, Bush DE, Ziegelstein RC. The significance of depression in older patients after myocardial infarction. J Am Geriatr Soc 2002;50:817-822.

157. Applegate WB, Blass JP, Williams TF. Instruments for the functional assessment of older patients. N Engl J Med 1990;322:1207-1214.

158. Robbins J, Hirsch C, Whitmer R, Cauley J, Harris T. The association of bone mineral density and depression in an older population. J Am Geriatr Soc 2001;49:732-736.

159. Han B. Depressive symptoms and self-rated health in community-dwelling older adults: a longitudinal study. J Am Geriatr Soc 2002;50:1549-1556.

160. Katz IR. Depression and frailty: the need for multidisciplinary research. Am J Geriatr Psychiatry 2004;12:1-6.

161. Fried L, Walston J. Frailty and failure to thrive. In: Hazzard W, Blass J, Ettinger. W, Halter J, Ouslander J, editors. Principles of Geriatric Medicine and Gerontology. 5 ed. New York, USA: McGraw-Hill, 2003:1487-1502.

162. Bergman H, Beland F, Karunananthan S, Hummel S, Hogan D, Wolfson C. Développement d'un cadre de travail pour comprendre et étudier la fragilité. Gérontologie et societé 2004;109:15-29.

163. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-156.

164. Ferrucci L, Penninx BW, Volpato S, Harris TB, Bandeen-Roche K, Balfour J, et al. Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc 2002;50:1947-1954.

165. Reding M, Haycox J, Blass J. Depression in patients referred to a dementia clinic. A three-year prospective study. Arch Neurol 1985;42:894-896.

166. Jorm AF, van Duijn CM, Chandra V, Fratiglioni L, Graves AB, Heyman A, et al. Psychiatric history and related exposures as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 Suppl 2:S43-47.

167. Alexopoulos GS, Meyers BS, Young RC, Mattis S, Kakuma T. The course of geriatric depression with "reversible dementia": a controlled study. Am J Psychiatry 1993;150:1693-1699.

168. Allen GM, Hickie I, Gandevia SC, McKenzie DK. Impaired voluntary drive to breathe: a possible link between depression and unexplained ventilatory failure in asthmatic patients. Thorax 1994;49:881-884.

169. Mintz J, Mintz LI, Arruda MJ, Hwang SS. Treatments of depression and the functional capacity to work. Arch Gen Psychiatry 1992;49:761-768.

170. Wells KB, Burnam MA, Rogers W, Hays R, Camp P. The course of depression in adult outpatients. Results from the Medical Outcomes Study. Arch Gen Psychiatry 1992;49:788-794.

171. Von Korff M, Ormel J, Katon W, Lin EH. Disability and depression among high utilizers of health care. A longitudinal analysis. Arch Gen Psychiatry 1992;49:91-100.

172. Ormel J, Von Korff M, Van den Brink W, Katon W, Brilman E, Oldehinkel T. Depression, anxiety, and social disability show synchrony of change in primary care patients. Am J Public Health 1993;83:385-390.

173. Bruce ML, Leaf PJ. Psychiatric disorders and 15-month mortality in a community sample of older adults. Am J Public Health 1989;79:727-730.

174. Bruce ML, Leaf PJ, Rozal GP, Florio L, Hoff RA. Psychiatric status and 9-year mortality data in the New Haven Epidemiologic Catchment Area Study. Am J Psychiatry 1994;151:716-721.

175. Murphy JM, Monson RR, Olivier DC, Sobol AM, Leighton AH. Affective disorders and mortality. A general population study. Arch Gen Psychiatry 1987;44:473-480.

176. Armenian HK, Pratt LA, Gallo J, Eaton WW. Psychopathology as a predictor of disability: a population-based follow-up study in Baltimore, Maryland. Am J Epidemiol 1998;148:269-275.

177. Gallo JJ, Rabins PV, Lyketsos CG, Tien AY, Anthony JC. Depression without sadness: functional outcomes of nondysphoric depression in later life. J Am Geriatr Soc 1997;45:570-578.

178. Turner RJ, Noh S. Physical disability and depression: a longitudinal analysis. J Health Soc Behav 1988;29:23-37.

179. Ormel J, Vonkorff M, Oldehinkel AJ, Simon G, Tiemens BG, Ustun TB. Onset of disability in depressed and non-depressed primary care patients. Psychol Med 1999;29:847-853.

180. Covinsky KE, Kahana E, Chin MH, Palmer RM, Fortinsky RH, Landefeld CS. Depressive symptoms and 3-year mortality in older hospitalized medical patients. Ann Intern Med 1999;130:563-569.

181. Parmelee PA, Lawton MP, Katz IR. The structure of depression among elderly institution residents: affective and somatic correlates of physical frailty. J Gerontol A Biol Sci Med Sci 1998;53:M155-162.

182. Kennedy GJ, Kelman HR, Thomas C. The emergence of depressive symptoms in late life: the importance of declining health and increasing disability. J Community Health 1990;15:93-104.

183. Blazer DG. Impact of late-life depression on the social network. Am J Psychiatry 1983;140:162-166.

184. Mussolino ME, Jonas BS, Looker AC. Depression and bone mineral density in young adults: results from NHANES III. Psychosom Med 2004;66:533-537.

185. Murphy E. The prognosis of depression in old age. Br J Psychiatry 1983;142:111-119.

186. Schulz R, Drayer RA, Rollman BL. Depression as a risk factor for non-suicide mortality in the elderly. Biol Psychiatry 2002;52:205-225.

187. Geerlings SW, Beekman AT, Deeg DJ, Twisk JW, Van Tilburg W. Duration and severity of depression predict mortality in older adults in the community. Psychol Med 2002;32:609-618.

188. Preville M, Boyer R, Hebert R, Bravo G, Seguin M. Correlates of suicide in the older adult population in Quebec. Suicide Life Threat Behav 2005;35:91-105.

189. Birrer RB, Vemuri SP. Depression in later life: a diagnostic and therapeutic challenge. Am Fam Physician 2004;69:2375-2382.